ClinVar Miner

Submissions for variant NM_001135651.3(EIF2AK2):c.398A>T (p.Tyr133Phe)

dbSNP: rs1573029592
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network, NIH RCV000991217 SCV001142597 uncertain significance EIF2AK2-related disorder 2019-07-26 criteria provided, single submitter clinical testing Testing for this patient was performed at Ambry. Given the variant is a de novo missense variant, absent in population databases, and unpublished cohort data suggest it is associated with specific neurologic phenotypes, this variant is classified as a variant of uncertain significance. The variant occurred de novo in a patient with neurologic phenotype. The variant is absent in gnomAD. Metrics indicate adequate coverage. As of 9/12/19, there were no published cases of disease causing variants in the EIF2AK2 gene. The EIF2AK2 gene has no established gene-disease association. The gene has a role in the EIF2B pathway, which has been associated with vanishing white matter leukoencephalopathies. However, unpublished laboratory cohort data has identified other unrelated patients with similar neurologic phenotypes to suggest that de novo missense variants are implicated in disease.
Ambry Genetics RCV001266299 SCV001444472 uncertain significance Inborn genetic diseases 2018-11-30 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV001093623 SCV001468564 uncertain significance Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome 2020-12-18 criteria provided, single submitter curation This variant is interpreted as a variant of uncertain significance for Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, autosomal dominant The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); de novo variant (PS2 downgraded to moderate); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting).
OMIM RCV001093623 SCV001250815 pathogenic Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome 2022-02-10 no assertion criteria provided literature only

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